Dr Catherine Lawrence
University of Manchester
Zinc deficiency drives inflammation-dependent cognitive decline in Alzheimers disease
Zinc (Zn2+) deficiency affects up to 2 billion people world-wide, and is particularly common in aged individuals. Low levels of Zn2+ are suggested to contribute to the worsening of Alzheimers disease (AD), and there is some evidence that dietary Zn2+ supplements may be protective. Inflammation is also known to contribute to the progression of AD. The NLRP3-inflammasome complex is one of the most important regulators of inflammation, and is central to the development of inflammation, pathology and memory deficits in a mouse model of AD. The overall aim of this research is to build upon our preliminary data establishing a link between Zn2+ deficiency and NLRP3 inflammasome activation. Using the APP/PS1 transgenic mouse model of AD we will examine the effects of a Zn2+ deficient diet on behaviour, memory and inflammation. We will breed APP/PS1 mice in which the gene for NLRP3 has been deleted and thus we will determine whether the effects of Zn2+ deficiency in the AD model occur via the NLRP3 inflammasome. The outcome of this research could be the realisation that there is a cohort of AD patients whose lives could be improved by the simple addition of a Zn2+ supplement to their diets. The experiments in this proposal may also provide further evidence that the process of inflammation represents a therapeutic target in AD.